ArticleOrphanet journal of rare diseases2019
Late-onset thymidine kinase 2 deficiency: a review of 18 cases.
Article in Orphanet journal of rare diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Advances in Primary Mitochondrial Diseases: Diagnosis, Natural History Studies and Clinical Trials.Genes · 2026Review
- Nucleoside therapy for thymidine kinase 2 deficiency: Long-term outcomes from a Brazilian cohort.Journal of neuromuscular diseases · 2026Article
- Exploring Outcome Measures for Mitochondrial Myopathies; Insights From a Longitudinal Study on TK2 Deficiency.Journal of inherited metabolic disease · 2026Article
- Disease burden of untreated thymidine kinase 2 deficiency: insights from a large patient dataset.Brain communications · 2026Article
- Efficacy and safety of pyrimidine nucleos(t)ide therapy in thymidine kinase 2 deficiency.Brain communications · 2026Article
- Pyrimidine Nucleos(t)ide Therapy in Patients With Thymidine Kinase 2 Deficiency: A Multicenter Retrospective Chart Review Study.Neurology · 2025Observational
- Novel biallelic TK2 mutations cause mitochondrial DNA depletion syndrome with infantile early-onset lipid storage myopathy.Orphanet journal of rare diseases · 2025Article
- Clinical and molecular spectrum of TK2-deficiency: a large Brazilian cohort.Scientific reports · 2025Article
- Clinical and Genetic Analysis of Patients With TK2 Deficiency.Neurology. Genetics · 2024Article
- Deoxyguanosine kinase deficiency: natural history and liver transplant outcome.Brain communications · 2024Article
- Pearls & Oy-sters: Case Report of a Patient With Adult-Onset Thymidine Kinase 2 Gene Deficiency.Neurology · 2023Article
- Reversible cardiac function and left ventricular hypertrophy in a Chinese man with mitochondrial myopathy: a case report.BMC cardiovascular disorders · 2023Article
- Review
- Serum GDF-15 Levels Accurately Differentiate Patients with Primary Mitochondrial Myopathy, Manifesting with Exercise Intolerance and Fatigue, from Patients with Chronic Fatigue Syndrome.Journal of clinical medicine · 2023Article
- Pathological Features in Paediatric Patients with TK2 Deficiency.International journal of molecular sciences · 2022Article
- Muscle MRI characteristic pattern for late-onset TK2 deficiency diagnosis.Journal of neurology · 2022Article
- Entecavir competitively inhibits deoxyguanosine and deoxyadenosine phosphorylation in isolated mitochondria and the perfused rat heart.The Journal of biological chemistry · 2022Article
- Case Report: Thymidine Kinase 2 (TK2) Deficiency: A Novel Mutation Associated With Childhood-Onset Mitochondrial Myopathy and Atypical Progression.Frontiers in neurology · 2022Article
- Advances in Thymidine Kinase 2 Deficiency: Clinical Aspects, Translational Progress, and Emerging Therapies.Journal of neuromuscular diseases · 2022Review
- Clinical, Histological, and Genetic Features of 25 Patients with Autosomal Dominant Progressive External Ophthalmoplegia (ad-PEO)/PEO-Plus Due toJournal of clinical medicine · 2021Article
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Authors and funding
24 authors at 12 institutions in 2 countries.
Funding
Abstract
backgroundTK2 gene encodes for mitochondrial thymidine kinase, which phosphorylates the pyrimidine nucleosides thymidine and deoxycytidine. Recessive mutations in the TK2 gene are responsible for the 'myopathic form' of the mitochondrial depletion/multiple deletions syndrome, with a wide spectrum of severity.
methodsWe describe 18 patients with mitochondrial myopathy due to mutations in the TK2 gene with absence of clinical symptoms until the age of 12.
resultsThe mean age of onset was 31 years. The first symptom was muscle limb weakness in 10/18, eyelid ptosis in 6/18, and respiratory insufficiency in 2/18. All patients developed variable muscle weakness during the evolution of the disease. Half of patients presented difficulty in swallowing. All patients showed evidence of respiratory muscle weakness, with need for non-invasive Mechanical Ventilation in 12/18. Four patients had deceased, all of them due to respiratory insufficiency. We identified common radiological features in muscle magnetic resonance, where the most severely affected muscles were the gluteus maximus, semitendinosus and sartorius. On muscle biopsies typical signs of mitochondrial dysfunction were associated with dystrophic changes. All mutations identified were previously reported, being the most frequent the in-frame deletion p.Lys202del. All cases showed multiple mtDNA deletions but mtDNA depletion was present only in two patients.
conclusionsThe late-onset is the less frequent form of presentation of the TK2 deficiency and its natural history is not well known. Patients with late onset TK2 deficiency have a consistent and recognizable clinical phenotype and a poor prognosis, due to the high risk of early and progressive respiratory insufficiency.
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